The Core Biochemistry Laboratory will be a major resource for the integration of the individual studies proposed in this Program Project. It will provide a uniform set of enzyme and immunoassays for samples submitted by each of the subcomponents. The Core Laboratory will also be a source of purified proteins and enzymes including calmodulin, calmodulin regulated enzymes, protein kinases and phosphatases, as well as immunoreagents for a variety of studies of individual investigations. The set of enzymes and proteins to be analyzed in all samples submitted to the Core was selected to test the hypothesis that alterations in the calcium signalling machinery are essential components in the neurodegeneration of Alzheimer's disease. Correlation of data obtained from uniform assays performed on normal and AD human tissues will test this hypothesis directly. Comparison of these results with analyses of samples from experimental animals and cultured cells treated in various ways, may permit the identification of possible factors (i.e., ischemic events, beta- amyloid production, glucocorticoid overproduction) which may trigger the biochemical alterations in Ca2+ regulation leading to neuronal cell death.